A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS.

OBJECTIVE: To compare the efficacy, tolerability, and safety of IV methylprednisolone (IV MP) vs oral methylprednisolone (oMP) at equivalent high doses in patients with multiple sclerosis (MS) experiencing a recent relapse. METHODS: Patients with a clinical relapse within the previous 2 weeks and at least 1 gadolinium (Gd)-enhancing lesion on a screening brain MRI scan were included. Forty patients with MS were randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients). Expanded Disability Status Scale (EDSS) and brain MRI (dual-echo and postcontrast T1-weighted scans) were assessed at baseline and at weeks 1 and 4. The study primary research question (endpoint) was to compare the efficacy of the 2 treatment routes in reducing the number of Gd-enhancing lesions after 1 week from treatment initiation. Secondary outcomes were safety, tolerability, and clinical efficacy profiles of the 2 routes of administration. RESULTS: The 2 groups showed a reduction of Gd-enhancing lesions over time (p = 0.002 for oMP and p = 0.001 for IV MP) with a "non-inferiority effect" between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p < 0.001) without between-group difference at week 4. Both treatments were well-tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms. CONCLUSIONS: Oral methylprednisolone (oMP) is as effective as IV methylprednisolone in reducing gadolinium-enhancing lesions in patients with MS soon after an acute relapse with similar clinical, safety, and tolerability profiles. This study provides class III evidence that 1 g oMP x 5 days is not inferior to 1 g IV MP x 5 days in reducing the number of gadolinium-enhancing lesions over a period of 1 week (mean difference in lesion reduction comparing IV MP to oMP is -20%, 95% confidence interval -48% to + 5%).

Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.

BACKGROUND: A 24-week phase II trial has shown that 0.3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions. We assessed the effect of oral daily 0.3 and 0.6 mg laquinimod on MRI-monitored disease activity in a 36-week double-blind, placebo-controlled phase IIb study. METHODS: The study was done in 51 centres in nine countries. Inclusion criteria were one or more relapses in the year before entry and at least one gadolinium enhancing (GdE) lesion on screening MRI. Of 720 patients screened, 306 eligible patients were enrolled. Patients, aged 18-50 years, were randomly assigned to placebo (n=102), laquinimod 0.3 mg a day (n=98), or 0.6 mg a day (n=106). Brain MRI scans and clinical assessments were done at week -4, baseline, and monthly from week 12 to week 36. The primary outcome was the cumulative number of GdE lesions at weeks 24, 28, 32, and 36. The principal analysis of the primary endpoint was done on the intention-to-treat cohort. This study is registered with ClinicalTrials.gov, number NCT00349193. FINDINGS: Compared with placebo, treatment with laquinimod 0.6 mg per day showed a 40.4% reduction of the baseline adjusted mean cumulative number of GdE lesions per scan on the last four scans (simple means 4.2 [SD 9.2] vs 2.6 [5.3], p=0.0048); treatment with 0.3 mg per day showed no significant effects (3.9 [5.5] vs placebo, p=0.6740). Both doses of laquinimod were well tolerated, with some transient and dose-dependent increases in liver enzymes. A case of Budd-Chiari syndrome-ie, a thrombotic venous outflow obstruction of the liver-occurred after 1 month of exposure in a patient with underlying hypercoagulability who received 0.6 mg laquinimod. Anticoagulant treatment resulted in a decline of liver enzymes to normal without any clinical signs of hepatic decompensation. INTERPRETATION: In patients with relapsing-remitting multiple sclerosis, 0.6 mg per day laquinimod significantly reduced MRI-measured disease activity and was well tolerated.

The relationship between the theory of evolution and the social sciences, particularly psychology.

The application of the theory of evolution to human social behavior has, along with some illumination, produced friction that occasionally bursts into flame. In this paper we will examine the relationship between the theory of evolution and the social sciences, psychology in particular. We will identify some of the sources of friction between proponents and opponents of applying evolutionary theory to the social sciences, and we will suggest that listening carefully to both sides in the debate points the way to an enriched understanding of human social behavior.